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个人简介
During my Ph.D., I used a wide spectrum of molecular biology techniques and practiced standard methodologies in cell culture and mouse models. As part of my thesis, I used mouse models to study the effects of monoclonal antibodies against a molecular chaperon (HSP90) on cancer metastasis in melanomas. We were among the first teams, which have shown that HSP90 is secreted from cancer cells and plays a significant role during cancer metastasis by modifying the Extra Cellular Matrix. Moreover, we also showed that the inhibition of eHSP90 using monoclonal antibodies has a significant impact on the growth and the metastatic potential of cancer cells and thus is eHSP90 is a very important new drug target.
During my first postdoctoral research project in the Laboratory of Chemical Carcinogenesis and Genetic Toxicology, Institute of Biological Research & Biotechnology NHRF I studied the mechanisms of carcinogenesis induced by chemical or physical agents of environmental relevance, focusing particularly on the study of DNA damage, its repair and cellular responses to it, as well as their modulation by carcinogens such as benzopyrene and others polycyclic aromatic hydrocarbons. We showed that DNA damage and the subsequent S-phase arrest is an ambiguous mechanism, which might not always result in repairing DNA damage but also increase the genomic instability, and thus it should be handled with extra care when translated into the clinic.
During my second postdoctoral research in the laboratory of Dr. Efstratiadis at Biomedical Research Foundation of the Academy of Athens I continued using mouse models as a tool in cancer therapeutics. I also used extensively molecular cloning and expression systems to generate cancer cell lines with Knocked-in genes of interest, to analyze their role in carcinogenesis. We were among the first teams that generated their own Knock-in mouse model for pancreatic cancer which showed the significance of c- Myc in Kras driven tumors. But since mouse genetics is the equivalent of tumor prevention in humans, we have further successfully proven the inhibitory role of anti- Myc small molecules as novel therapeutic approaches at least on pancreatic cancer. During this study I was involved in all the individual steps that are required in order that a successful preclinical study is completed. To be more specific, I tested novel anti-Myc compounds in vitro. I created human cancer cell-based xenografts and tested the efficacy in vivo; collected plasma for the pharmacokinetic analysis, and finally monitored using micro-PET/CT the efficacy of the compound in the pancreatic cancer mouse model. After our first publication, I continued studying in vitro and in vivo novel anti-Myc compounds and combinational therapeutic schemes using anti-Myc compounds in combination with other chemotherapeutic agents already established in the clinic. In order to create most relevant to the human disease models I generated Patient Derived Xenografts by orthotopically engrafting small pieces of human fresh pancreatic tumors into the pancreata of NOD/Scid/IL2γ-receptor null (NSG) mice mice. This approach drew the attention and funding from the Hellenic Company of Metastatic Liver Disease. Under this funding we proposed to perform an exome Sequencing and compare the PDX tumors with the original human tumors. This analysis will reveal the mutational profile of each tumor and will enable us to design a Personalized drug testing based on the mutations and the affected molecular pathways of each patient.
In NCI/NIH, as a research fellow in Dr. Pavlakis team I continued using Genetically Engineered Mouse Models of Pancreatic and Breast Cancer to explore the therapeutic role of immunotherapy with Interleukin 15(IL-15) and combinational chemotherapy on the treatment of these cancers. Moreover, using IL-15 immunotherapy in combination with surgery as a neoadjuvant therapeutic approach we were able to almost eradicate the metastatic disease in a syngeneic mouse model. Since the Natural Killer (NK) cells are stimulated by IL-15 we also plan to create Chimeric Antigen Receptor NK cells against pancreatic tumors using mesothelin as a target-protein and use adoptive cell transfer in combination with IL-15 immunotherapy. We also tested the therapeutic possibility of local delivery of IL-15 on breast cancer tumors using hydrogels as delivery systems, with impressive results. In this context we found that local delivery of IL-15 altered the cytokine milieu intratumorally, resulting to long term immunological memory against cancer by recruiting a novel Dendritic Cell population with antigen presenting abilities and monocytic origin. My research during COVID-19 era, changed gears to study the effects of the neutralization abilities of convalescent plasma. Therefore, in the labs of Dr. Pavlakis and Dr.Felber we have generated a pseudoviral SARS-COV-2 assay to measure the neutralization ability of human and monkey plasma against SARS-COV-2.
研究兴趣
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Cancer Researchno. 6_Supplement (2024): 4064-4064
Pharmaceuticsno. 3 (2023): 787-787
Pharmaceuticsno. 787 (2023): 787
Journal of Experimental & Clinical Cancer Researchno. 1 (2023): 1-20
Cancer Researchno. 7_Supplement (2023): 5082-5082
International journal of molecular sciencesno. 10 (2023): 8543-8543
Cell Reportsno. 5 (2023): 112501-112501
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